It is known that DPP-IV has various physiological functions in living body, especially has the action which inactivates Glucagon-like peptide-1 (GLP-1) by cleaving the terminal dipeptide (His-Ala) and decomposes some cytokines. That is, the resultant peptide is the receptor antagonist of GLP-1 and totally reduces the activity of GLP-1.
This GLP-1 has very important role in sugar metabolism. For example, (1) GLP-1 intensifies the secretion of insulin, (2) express genes which are indispensable for the secretion of insulin, (3) stimulate proliferation of β-cell, (4) suppresses secretion of glucagon, (5) suppresses the function about secretion and motility of digestive organs (especially, peristalsis), and (6) suppresses appetite. That is, GLP-1 restricts food ingestion, postpones the process of digestion and absorption, and raised the use of the sugar in blood.
Therefore, the inhibitor of DPP-IV can maintain the activity of GLP-1, so it is expected as a medicine to treat and prevent various diseases, especially non-insulin dependent diabetes mellitus (NIDDM).
Hitherto, such inhibitors of DPP-IV are known so far. For example in U.S. Pat. Nos. 6,011,155 and 6,124,305, 2-cyanopyrrolidine compounds having [3.1.1]bicyclo moiety like following are disclosed.
